The long-term goal of the proposed partnership is to develop, unify, refine and implement a new approach to quantitative ultrasound (QUS) imaging of biological tissues and mammary tumors by the quantification of tissue microstructure. In lay terms, if the research is successful, many breast abnormalities and lesions can be diagnosed without the need for a biopsy. The overall hypothesis of our partnership is that a set of QUS parameters can significantly improve breast lesion differentiation/classification. The primary QUS parameters to be exploited include attenuation, scatterer size, scatterer number density, and acoustic concentration (scatterer number density times their impedance change). Our goal in the first 5 years of this project is to lay the foundation for a new (possibly revolutionary but definitely evolutionary) diagnostic imaging capability through development, testing, and verification with simulations, phantoms, and in vitro and in vivo animal model experiments, as well as preliminary human subjecting testing. In the second 5 years we will extend the analysis beyond common breast lesions, begin Phase II clinical trials and work towards the creation of automated tools to assist in the diagnosis of breast abnormalities. The partnership is between engineers, acoustic physicists, statisticians and veterinary pathologists at UIUC and physicists, engineers, pathologists and radiologists at UW. The PI is William D. O'Brien, Jr. (UIUC), and functioning as the co-Pi is Timothy J. Hall (UW). Use of QUS imaging is medically significant because it offers a potentially real-time and noninvasive means of differentiation/classification tumor types and tracking their response to therapy. To this end, 5 specific aims are proposed, viz., 1) unify QUS algorithms with simulations, phantoms and animal tumor models in vivo, 2) associate acoustic microstructural measurements with anatomical scattering sources, 3) monitor the changes in QUS parameters with tumor growth in in vivo animal models, 4) compare tumors in human subjects with those in animal models, and 5) develop a major outreach activity.